Genetic variants associated with Crohn's disease.

Crohn's disease is an immune-related disorder characterized by inflammation of the gastrointestinal mucosa, which can occur in any area throughout the digestive tract. This life-long disease commonly presents with abdominal pain, diarrhea, vomiting, and weight loss. While the exact etiology of this disease is largely unknown, it is thought to arise from an interaction between microbial, immunological, and environmental factors in a genetically susceptible host, whereby the immune system attacks the intestine as it cross reacts against gut microbial antigens. The study of genetic variants associated with Crohn's disease has shed light on our understanding of disease pathophysiology. A large number of genetic variants identified in Crohn's disease are related to genes targeting microbial recognition and bacterial wall sensing, the most common being NOD2/CARD15 gene. This review will discuss the recent advance in our knowledge of genetic variants of this disease and how they influence the disease course and prognosis.

A multicenter study of the incidence and factors associated with redo Nissen fundoplication in children.

AIM: The objective of this study was to identify the incidence and factors associated with redo Nissen fundoplication in children. METHODS: After Institutional Review Board approval (5100277), data for children under 18 years of age from two children's hospitals with fundoplication performed between January 1994 and December 2010 were reviewed. Children with one fundoplication were compared to those with redos to identify factors associated with redo. Variables were compared using t-tests for continuous and chi-square tests for categorical variables. Logistic regression evaluated for independence. RESULTS: There were 823 patients and 54.7% were male. A redo fundoplication was required in 100 (12.2% of cohort); 82 had 1 redo, 14 had 2 redos, and 4 had 3 redos. Follow-up ranged from 0.01 to 16.9 years (median: 2.9 years). Factors associated with redo were: younger age at first fundoplication, (p=0.002), hiatal dissection (p<0.001), and male gender (p=0.008). Independent predictors of redo were: hiatal dissection at first fundoplication, OR: 8.45 (95% CI: 2.45-29.11), retching, OR: 3.59 (95% CI: 1.56-8.25) and younger age at first fundoplication, OR: 0.98 (95% CI: 0.97-0.98). CONCLUSION: The incidence of redo fundoplication in children is 12.2%. The risk of redo is significantly increased if patients are younger, have retching, and if the esophageal hiatus is dissected at the first fundoplication.

Need for a comprehensive medical approach to the neuro-immuno-gastroenterology of irritable bowel syndrome.

Irritable bowel syndrome (IBS) is defined by the Rome III criteria as symptoms of recurrent abdominal pain or discomfort with the onset of a marked change in bowel habits with no evidence of an inflammatory, anatomic, metabolic, or neoplastic process. As such, many clinicians regard IBS as a central nervous system problem of altered pain perception. Here, we review the recent literature and discuss the evidence that supports an organic based model, which views IBS as a complex, heterogeneous, inter-dependent, and multi-variable inflammatory process along the neuronal-gut axis. We delineate the organic pathophysiology of IBS, demonstrate the role of inflammation in IBS, review the possible differences between adult and pediatric IBS, discuss the merits of a comprehensive treatment model as taught by the Institute of Functional Medicine, and describe the potential for future research for this syndrome.

A comparison of presentation and management trends in acute pancreatitis between infants/toddlers and older children.

OBJECTIVES: Acute pancreatitis is a necroinflammatory disease that leads to 210,000 hospitalizations in the United States annually. Recent reports suggest that there may be important differences in clinical features between infants/toddlers and older children. Thus, in this study we make a direct comparison between the pediatric age groups in presentation and management trends of acute pancreatitis. PATIENTS AND METHODS: We examined all children (ages 0 to 20 years) admitted to Yale-New Haven Children's Hospital with pancreatitis between 1994 and 2007. RESULTS: Two hundred seventy-one cases met inclusion criteria for acute pancreatitis. Infants and toddlers manifested fewer signs and symptoms of abdominal pain, epigastric tenderness, and nausea compared with older children (43% vs 93%; 57% vs 90%; and 29% vs 76%, respectively; P < 0.05 for all comparisons). They were more likely to be diagnosed by serum lipase than by amylase and to undergo radiographic evaluation (P < 0.05). They had a longer hospital stay (19.5 vs 4 days; P < 0.05) and were less likely to be directly transitioned to oral nutrition (14% vs 71%; P < 0.05). CONCLUSIONS: Infants and toddlers with acute pancreatitis present with fewer classical symptoms and are managed differently from older children. We believe these data will be helpful in evaluating and understanding treatment practices in this age group.

The risk of Parkinson's disease in type 1 Gaucher disease.

In Gaucher disease, defective lysosomal glucocerebrosidase due to mutations in the GBA1 gene results in lysosomal accumulation of glucocerebroside in mononuclear phagocytes and a multisystemic phenotype. Observations of occurrence of Parkinson's disease in some patients with non-neuronopathic type 1 Gaucher disease (GD1) and their first degree relatives has led to the identification of GBA1 heterozygous mutations as a genetic risk factor for idiopathic Parkinson's disease (PD). However, the magnitude of risk of PD in patients with known GD1 has not been determined, and it is not known whether GD1/PD represents a specific sub-phenotype of GD1 with distinctive genotype/phenotype characteristics. We estimated the risk of PD in a cohort of 444 consecutively evaluated patients with GD1 compared to that in the general population. Eleven patients developed parkinsonian syndrome during a 12-year follow-up period. The adjusted life-time risk ratio of PD in GD1 compared to that in the general population was 21.4 [95% confidence interval (95% CI) 10.7-38.3], with a higher risk in men compared to women. In our cohort, GD1/Parkinson's disease phenotype (GD1/PD) was characterized by higher GD1 severity score, due to higher incidence of avascular osteonecrosis. The clinical spectrum of PD varied from mild to potentially life-threatening disease. All but one patient with GD1/PD phenotype had at least one N370S GBA1 allele. In conclusion, compared to the general population, patients with GD1 have an almost 20-fold increased life-time risk of developing PD.

Recurrent acute pancreatitis in a child with primary hyperparathyroidism.

Hypercalcemia is an important etiology to consider in the evaluation of acute pancreatitis. Not only is it a treatable cause, but understanding the basis for this etiology may provide new insight into the common biochemical mechanisms involved in the pathogenesis of pancreatitis. We report a case of an 11-year-old girl with hypercalcemia due to primary hyperparathyroidism who developed recurrent pancreatitis. We review clinical and experimental data that implicate hypercalcemia as the cause and discuss mechanisms for the association.